Drug intelligence / Profile preview

cisplatin + nintedanib + pemetrexed

Development stage
Discontinued
Lead developer
Boehringer Ingelheim
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination regimen consisting of three drugs—cisplatin, nintedanib, and pemetrexed—used primarily in the treatment of unresectable malignant pleural mesothelioma. Cisplatin is a platinum-based chemotherapy agent that causes DNA crosslinking and apoptosis in cancer cells. Pemetrexed is an antifolate antineoplastic agent that inhibits enzymes involved in folate metabolism and DNA synthesis, thereby preventing cancer cell replication[7][10]. Nintedanib is an oral small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR α/β), fibroblast growth factor receptors (FGFR 1-3), as well as Src and Abl kinases; these pathways are implicated in tumor angiogenesis, proliferation, and metastasis[1][2][9]. The combination has been studied as first-line therapy for patients with unresectable epithelioid malignant pleural mesothelioma. Clinical trials have shown improved progression-free survival compared to standard chemotherapy alone[2][5].

02

Targets

DNADHFR (Dihydrofolate reductase)FGFR1 (Fibroblast growth factor receptor 1)FGFR2 (Keratinocyte growth factor receptor)FGFR3 (Fibroblast growth factor receptor 3)GART (GAR transformylase)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)TS (Thymidylate synthase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)SRC (Proto-oncogene tyrosine-protein kinase Src)

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